The present disclosure relates to a flow control system for a magnetically driven micropump for handling small fluid volumes. In particular, the present disclosure relates to a micropump including a magnetically actuated membrane to transfer fluids, and an innovative flow control system therefor utilizing a membrane designed particularly therefor.
The field of microfluidics generally encompasses handling very small fluid volumes on the order of several nanoliters. Microfluidics has increasingly important applications in such fields as life sciences and chemical analysis. Microfluidics devices, also known as micromechanical systems (MEMS), include devices for fluid control, fluid measurement, medical testing, DNA and protein analysis, in vivo drug delivery, and other biomedical applications.
Typical fluid flow rates of micropumps range from approximately 0.1 microliter per minute to several (80-180) milliliters per minute. Flow rates on this order are useful in applications such as disposable micro total analysis systems (μTAS) or lab-on-a-chip (LOC) for chemical and biological analysis, point of care testing (POCT) for medical diagnostic testing, implantable drug delivery systems for medications (such as insulin) requiring a fine degree of regulation and precise control, and cardiology systems for blood transport and pressurization.
Since most of MEMS processing techniques evolved from microelectronics, the first silicon micropump was based on a piezoelectric actuation of a thin membrane in 1980s primarily for use in the controlled insulin delivery systems. This work demonstrated the feasibility of silicon-based micropump and inspired extensive research on silicon micropumps. Also, several commercially available implantable silicon micropumps were reported for insulin delivery and therapeutic agents dispensing through pharmaceutical and clinical therapy fields.
Recently, a number of polymeric materials and new microfabrication techniques, such as soft lithography, microstereolithography, micromolding and polymeric surface micromachining, have been investigated and developed for a growing trend of low cost, integrated and miniaturized disposable μTAS applications. Many polymeric materials including plastics and elastomers have been increasingly incorporated into other microdevices as substrates, structural membranes, and functional membranes due to their excellent mechanical properties, good chemical resistance, and low fabrication cost. Among the most popular polymers, polydimethylsiloxane (PDMS) has been extensively utilized in microfluidic devices because of excellent biocompatibility, simple fabrication process (molding and reversible bonding) and optical transparency (facilitating monitoring and interrogating) as well as elasticity (good sealing and connecting).
Silicon-based and plastic-based MEMS valveless micropumps are taken as an example to compare with a PDMS-based micropump. The fabrication process of the silicon-based MEMS micropump involved three subsequent Deep Reactive Ion Etching (DRIE) steps and one silicon-glass anodic bonding step while LIGA, microinjection, or hot embossing molding and multiple thin plate assembly with adhesives or bolts was involved for the plastic pumps. On the other hand, for a PDMS-based micropump only multilayer soft lithography processes and PDMS-PDMS bonding techniques are usually required. From the fabrication cost point of view, a MEMS PDMS-based micropump is considerably lower than the former two types of micropumps.
There is an increasing interest for embedded systems with feedback control and subsequent delivery of more than one drug, handling small, precise (accurate) volumes of fluids. Such applications include drug delivery pain management and micro total analysis systems (μTAS). A. Manz, N. Graber, and H. Widmer, “Miniaturized total chemical analysis systems: a novel concept of chemical sensing,” Sensors and Actuators B, vol. 1, pp. 244-248, 1990. Micropumps are one of the main components of these systems and are often the limiting factor for size, weight and cost. For this purpose, a number of micropumps have been designed and fabricated utilizing a variety of different technologies.
These include modifications and downsizing, or scaling down, the current pumps used for insulin delivery. Commercial applications involving active micropumps, such as insulin delivery systems, are typically based on classical electrical motors in designs such as syringe pumps or peristaltic pumps. These designs are cost-effective, and trials have been performed to reduce their size. C. Koch, V. Remcho, and J. Ingle, “PDMS and tubing-based peristaltic micropumps with direct actuation,” Sensors and Actuators B, vol. 135, pp. 664-670, 2009. However, the size of the electric motors necessary for delivering the desired forces prevents miniaturization below the 40-50 mm range. This severely limits the scope of applications to large and bulky drug delivery systems.
Silicon-based MEMS micropumps have been used, mostly by employing piezoelectric actuation. H. van Lintel, F. V. de Pol, and S. Bouwstra, “A piezoele ctric micropump based on micromachining of silicon,” Sensors and Actuators A, vol. 15, p. 153-167, 1988; N. Nguten, Nguyen, X. Huang and T. Chuan, “MEMS-micorpumps: a review,” Journal of Fluids Engineering, vol. 124, p. 384-392, 2002; A. Acevedo, Creation of Dual Chamber Micropump Using Rapid Prototyping, Milwaukee School of Engineering. However, the material cost of silicon and related fabrication issues burden its use.
Lower cost micropumps have been attempted using materials such as plastic, see, e.g., “Small, powerful, light, precise: micro diaphragm pumps made of plastics,” March 2009, [online] http://www.thinxxs.com/main/produkte/micropumps.html; “Bartels micropumps,” April 2009, [online] http://www.bartelsmikrotechnik.de/index.php/micropumps.html; and “Precision products,” March 2009, [online] http:/www.starm.jp/eng/products/precision/index/html, PDMS or PDMS+PMMA, see, e.g., O. Jeong, S. Park, S. Yang, and J. Pak, “Fabrication of a peristaltic PDMS micropump,” Sensors and Actuators A, vol. 123-124, pp. 453-458, 2005; C. Yamahata, C. Lotto, E. Al-Assaf, and M. Gijs, “A PMMA valveless micropump using electromagnetic actuation,” Microfluid Nanofluid, vol. 1, pp. 197-207, 2005; and T. Pan, S. McDonald, E. Kai, and B. Ziaie, “A magnetically driven PDMS micropump with ball check check-valves,” J. Micromech. Microeng, vol. 15, pp. 1021-1026, 2005.
Efforts at disposability have been made. See, e.g., F. Trenkle, S. Haeberle, and R. Zengerle, “Normally-closed peristaltic micropump with re-usable actuator and disposable fluidic chip,” Sensors and Actuators B 54, Science Direct, vol. 1, pp. 1515-1518, 2009; S. Ha, W. Cho, and Y. Ahn, “Disposable thermo-pneumatic micropump for bio lab-on-a-chip application,” Microelectronic Engineering, vol. 86, pp. 1337-1339, 2011; and R. Irawan, S. Swaminathan, P. Aparajita, and S. Tjin, “Fabrication and performance testing of disposable micropump suitable for microfluidic chip,” in Intl. Conf. on Biomedical and Pharmaceutical Engineering, Orchard Hotel, Singapore, December 2006, pp. 252-255. However, the PDMS pumps described are based on expensive microfabrication techniques, which require costly equipment that utilizes an inherently slow process. This limits the ability for manufacturers to mass-produce these types of pumps.
Some studies have focused specifically on reducing fabrication costs by utilizing clever polymer based designs which can be produced with standard fabrication techniques. In M. Zhu, P. Kirby, M. Wacklerle, M. Herz, and M. Richter, “Optimization design of multi-material micropump using finite element method,” Sensors and Actuators A, vol. 149-1, pp. 130-135, 2009, piezoelectric actuation was used to supply up to 1.8 mL/min with 44×17×8 mm3 pumps. In S. Bohm, W. Olthuis, and P. Bergveld, “A plastic micropump constructed with conventional techniques and materials,” Sensors and Actuators A, vol. 77-3, pp. 223-228, 1999, both electromagnetic and piezoelectric actuators were used to supply up to 1.8 mL/min with a 10×10×8 mm3 pump (electromagnetic version) and 2.1 mL/min with a 12×12×2 mm3 pump (piezo version). They were successful in reducing manufacturing costs but not to the point desired for disposable systems. In the case of piezoelectric actuators, piezoelectric materials are expensive and they require high operating voltages. This requires the use of specialized, expensive, and bulky electronics, which is especially difficult to incorporate in embedded applications. In the case of electromagnetic actuators, an expensive and bulky coil is required inside the pump. In both cases, electrodes and supply wiring are needed in the pump body itself, which increases the volume and price of the pump.
For drug delivery and μTAS applications, disposable pumps would be especially desirable since it would eliminate the need for cleaning and sterilizing after each use and would decrease the risk of chemical impurities or biological contamination. Unfortunately, the relatively high cost of micropumps today prevents disposable use, which strongly limits the scope of their applications.
Another feature common to all of the aforementioned micropumps is an open-loop control system with flow rates dependent on the driving frequency alone. This often leads to a lack of reproducibility and a lack of flow rate predictability. As a result, the ability to supply precise flow rates and doses is severely impeded making them poorly suited for applications such as drug delivery.
Thus, a problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump having a disposable subassembly that can be readily mated with an actuation assembly.
Yet another problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump that can be readily configured for use in medical applications.
Still a further problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump having a relative low cost of manufacture while at the same time providing a sterile product having disposable parts.
An additional problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump having the requisite precision governing volumetric flowrate, which is particularly important in medical applications.
Another problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump that prevents reverse flow or backflow, which is particularly important in medical applications.
An even further problem associated with devices that precede the present disclosure is that they do not provide, in combination with the other features and advantages disclosed herein, a flow control system for use with a micropump having an efficient power-consumption profile, thereby maximizing battery life.
There is a demand, therefore, to overcome the foregoing problems while at the same time providing a flow control system for use with a micropump that is relatively low in cost to manufacture and yet possesses extended durability.